X-ray diffraction and electron microscopy will be used to study multisubunit enzymes that are of central importance in metabolism. Our objectives are: (1) To compute a three-dimensional reconstruction of the electron density of glutamine synthetase at low resolution from micrographs of helical aggregates of the molecule; (2) To determine the quaternary structure of RNA polymerase and ribulose diphosphate carboxylase using combined x-ray diffraction and electron microscopy; (3) To solve the structure of glutamine synthetase and to interpret the structure in terms of the atomic basis of relation of metabolism; and (4) To determine the atomic structure of aldolase, and to interpret the structure in terms of its mechanism of action. Our long range goals are to provide the basis for understanding normal and pathological metabolism at the molecular level and to lay a foundation for treatment of metabolic disorders.